Glucose is one of the most important medically significant analytes in human body fluids. For this reason, reference is made to glucose in the disclosure as an example for a medically significant analyte in a human or animal body fluid without limiting the general scope of the invention.
Continuous monitoring of the blood glucose concentration, during which measuring values are obtained, for example, every few minutes, are known according to the prior art under the term, “continuous monitoring,” for example from U.S. Pat. No. 6,272,480 or European Pat. No. EP 1102194A2. The aim of these applications is to administer the insulin doses required for the treatment of diabetes at optimal points, in time in optimal quantities in order to maintain the blood sugar level of a diabetic within narrow limits, as is the case in a healthy person.
The blood glucose concentration of a patient is of extreme medical significance. According to the results of studies, extremely serious long-term consequences of diabetes mellitus (for example loss of eyesight due to retinopathy) can be prevented by careful monitoring of the blood sugar level and by keeping the blood sugar level within narrow limits.
Systems for the investigation and monitoring of glucose metabolism have a sensor module that facilitates continuous or quasi-continuous measurement of the analyte concentration. Suitable sensors can, for example, be implanted directly into subcutaneous fatty tissue or blood vessels. It is also feasible to implant catheters by means of which an exchange between a dialysate and the surrounding body fluid is utilized for collecting analytes. The dialysate can be transported via microfluidics to a sensor that is situated outside the body. In principle, it is also feasible to measure analyte concentrations by means of a non-invasive sensor that is, for example, glued to the skin.
Known systems for the monitoring of the glucose concentration aim to counteract a dangerous increase of the blood glucose concentrations in due time by administering a dose of insulin. For this purpose, it is often desired to be able to predict future blood glucose concentrations over a period of time of approximately half an hour on the basis of previously determined measuring values such that a dangerous increase of the glucose concentration can be prevented by timely administration of a dose of insulin, e.g., U.S. Pat. No. 6,272,480.
To allow an analyte concentration to be determined from a raw or measuring signal, for example an electrical current, of a sensor, the sensor that is employed for this purpose must be calibrated in a resource-consuming fashion. An underlying prerequisite for successful calibration is that raw signals that are output by the sensor show a sufficient correlation with reference values of the analyte concentration that are determined on body fluid samples obtained from the body. In particular in the case of implanted sensors, the measuring sensitivities can change markedly over time such that renewed in-vivo calibration may be required in regular intervals. Problems of the calibration of implantable sensors and approaches to solutions thereof are summarized in the publication, G. Velho et al., “Strategies for calibrating a subcutaneous glucose sensor”, Biomed. Biochim. Acta, pp. 957-964, vol. 48 (1989).
In principle, calibration problems might be prevented by concomitantly measuring an internal standard. This approach is described in the publication, A. Sieg et al, “Electroosmosis in Transdermal Iontophoresis: Implications for Noninvasive and Calibration-Free Glucose Monitoring,” Biophysical Journal, pp. 3344-3350, vol. 87 (2004).